Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle is a target organ during sepsis; nevertheless, there is no evidence of a possible free radical overproduction with tissue damage in this situation. We studied Sprague Dawley female rats in two groups: a septic group with cecal ligation and double cecal perforation and a control group that was sham operated. Hind limb adductor muscles spontaneous chemiluminescence was measured at 2, 4, 6, 12, 24, and 30 hr after the surgical procedure as the expression of oxygen excited species generation. Muscle samples were also taken and activity of the principal antioxidant enzymes--superoxide dismutase (SOD), catalase, and glutathione peroxidase--as well as myeloperoxidase, an index of neutrophil infiltration was determined. CPK seric assays at 12 and 24 hr were used to reflect muscle injury and revealed high levels. Previously administered bovine superoxide dismutase was employed to prevent or attenuate oxidative stress. The results showed that light emission by rat skeletal muscle doubled from 4 to 12 hr of sepsis and could be attenuated with SOD pretreatment. Observed changes may be attributed to the production of oxygen free radicals that do not depend on local neutrophil infiltration. The detoxifying antioxidant enzyme activities in skeletal muscle were diminished (Mn SOD 46% at 6 hr, catalase 83% at 12 hr glutathione peroxidase 55% at 12 hr), which would also facilitate muscle septic damage.
 ...
PMID:Oxidative stress in skeletal muscle during sepsis in rats. 838 98

Chronic granulomatous disease of childhood is an inheritable disorder of phagocytic cell respiratory burst resulting in recurrent, life-threatening, catalase-positive infections. The lung is the most common site of infection, and pulmonary disease is the primary cause of death in greater than 50% of children with chronic granulomatous disease. Still, the role of surgery in management of this disease remains undefined. Between 1974 and 1990, 19 patients with chronic granulomatous disease required 31 thoracic interventions at our institution. Patients ranged in age from 2.5 to 27 years (mean age, 15 years). Seventeen of 19 patients (89%) had had previous pulmonary infections. Patients presented as toxic (temperature > 38.5 degrees C, chest pain, and cough) in 22 instances before the 31 procedures. Aggressive surgical intervention for diagnosis and extirpation of localized infections was undertaken with lobectomy/pneumonectomy with or without other procedures (5), bisegmentectomy (2), segmentectomy with or without other procedures (5), or wedge with or without other procedures (13). In five instances, an empyema was drained; a chest tube for a sterile collection was placed in one instance. There was one intraoperative death, and 3 patients died 22 to 600 days postoperatively with overwhelming sepsis. The mean hospitalization was 101 days (range, 24 to 600 days). Wound complications occurred in 5 patients, requiring 17 separate anesthetic debridements. A change in therapy was dictated by the results of the procedure in 23 of 31 instances (74%). Thoracic surgeons must be aware of this rare cause of immunosuppression in these children and, due to the unusual nature of the pulmonary infections, should follow an aggressive approach in their diagnosis and management.
 ...
PMID:Surgical management of pulmonary infections in chronic granulomatous disease of childhood. 846 36

Time course changes in hepatic mitochondrial and peroxisomal fatty acid oxidative capacities, as well as changes in the related enzyme activities, were investigated in rats with sepsis induced by cecal ligation and puncture. Palmitoyl-L-carnitine oxidation was not altered, but carnitine palmitoyl-transferase (CPT) dependent palmitoyl-CoA (plus L-carnitine) oxidation was slightly increased in the liver mitochondria of the septic rats. Hepatic CPT activity, being the rate-limiting step of mitochondrial beta-oxidation, was also enhanced by sepsis. In contrast, cyanide-insensitive peroxisomal beta-oxidation and the carnitine acetyltransferase and catalase activities associated with the peroxisomal-enriched fraction were markedly reduced by abdominal sepsis. Cyanide-insensitive beta-oxidation in control livers showed optimal specificity for lauroyl- and myristoyl-CoA and this pattern remained unchanged by sepsis. However, oxidation rates were reduced for all acyl-CoA esters tested, being more pronounced with longer carbon chain length acyl-CoA substrates. These results indicate that in early sepsis, hepatic mitochondrial fatty acid oxidative capacity was increased, probably due to enhanced CPT activity, whereas peroxisomal beta-oxidation was seriously disturbed along with reduced catalase activity.
 ...
PMID:Rat liver peroxisomal and mitochondrial fatty acid oxidation in sepsis. 846 59

In gram-negative septicemia, endotoxin-induced free radicals probably damage the liver cells by membrane lipid peroxidation. Phosphotidylcholine hydroperoxide (PCOOH), a primary lipid peroxidation product can be applied as a parameter to measure the extent of liver damage. The protective effects of urinastatin and free radical scavengers, superoxide dismutase (SOD), and catalase against hepatic lipid peroxidation and tissue energy reserves in the liver during endotoxemia were evaluated in rats with gram-negative septicemia induced by cecal ligation and puncture (CLP). One hundred and sixty-five rats were divided into three groups. The first two groups consisted of 45 rats each. Group (1) was used for blood endotoxin level and liver function tests, group (2) for hepatic energy charge and PCOOH measurement, and group (3) (n = 75) for survival study. In each group, control animals received saline injection only. Urinastatin was injected twice intravenously through tail veins using 50,000 u/kg at 0 and 12 hr after CLP. SOD 90,000 u/kg and catalase 50,000 u/kg were given subcutaneously just before CLP and every 3 hr thereafter up to 24 hr. Liver and blood specimens were taken at time points 0, 12, and 24 hr after CLP. Increased concentration of PCOOH in liver denotes that endotoxemia can damage the liver by hepatocellular lipid peroxidation. Attenuation of lipid peroxidation, which correlated with liver enzyme leakage, was noted by finding significant decreased concentrations of PCOOH (P < 0.001), improvement in energy charge (P < 0.05), and survivability (P < 0.05) was seen in urinastatin or radical scavenger-treated groups. These results suggested that urinastatin has protective effect against free radical-induced lipid peroxidation probably by inhibiting proteases especially elastase, from polymorphonuclear leucocytes. SOD and catalase, which scavenged oxygen free radicals, also suppressed free radical-induced lipid peroxidation. Improvement in survivability was also seen in treated groups.
 ...
PMID:Effects of urinastatin and free radical scavengers on hepatic lipid peroxidation in endotoxemia. 876 68

Nitric oxide release is induced in many cells, including vascular endothelium, as part of the host response to inflammation. Nitric oxide synthase activity is increased in patients with sepsis, associated with increased oxidant demands and decreased antioxidant protection. We used a human vascular endothelial cell line to investigate the influence of antioxidants on nitric oxide synthase activity. Cells were cultured to confluence and incubated with interferon gamma, tumor necrosis factor, and lipopolysaccharide in the combined presence of the antioxidants ascorbic acid, Trolox, catalase, or superoxide dismutase, singly and in combination, for 48 h. Additionally, some cells were incubated with hypoxanthine-xanthine oxidase or a nitric oxide donor. Nitric oxide synthase activity was upregulated by cytokine exposure (p < .0005). Ascorbic acid and superoxide dismutase/ catalase resulted in decreased enzyme activity (p < .05). Superoxide anion release from xanthine oxidase caused increased activity (p < .05) and exogenous nitric oxide tended to suppress synthase activity. We suggest that antioxidants scavenge superoxide anion, enabling feedback inhibition of nitric oxide synthase activity by nitric oxide, and thus reducing enzyme activity. Exogenous nitric oxide also has a similar effect. Superoxide generation suppresses this feedback inhibition. This study has important implications in patients with sepsis in whom nitric oxide synthase inhibitor therapy is currently under investigation.
 ...
PMID:Regulation of nitric oxide synthase activity in cultured human endothelial cells: effect of antioxidants. 879 Oct 97

Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further evaluation as therapeutic agents for treatment or prevention of sepsis-related ARDS in humans.
 ...
PMID:Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. 882 94

It is impossible to imagine modern medicine today without indwelling devices of various kinds. The time that these implants or prostheses remain in the patient's body can vary from a few hours, e.g. intravenous catheter, to his entire life, e.g. hip prosthesis, heart valve. Besides the indisputable use and advantages of this type of medical intervention for the patient, e.g. saving his life or improving its quality, the associated complications should not be overlooked. One of the most frequent and significant complications of implant surgery is the manifestation of infection in the tissue around the implant. That infection occurs is not surprising since the indwelling devices predispose to bacterial and mycotic infection on the one hand and impede its eradication on the other. The consequences of infection for the patient may mean the loss of regained mobility and independence, hospitalization for sepsis, or even death. Microbes per se are not necessarily pathogenic, however, there are numerous virulence factors which affect the degree of pathogenicity of the microorganisms. These include, for example, various enzymes, (e.g. catalase, hyaluronidase, collagenase and other proteases), and specific surface structures, e.g. the polysaccharide capsules of pneumococci or the lipopolysaccharides of Gram negative bacteria, and the production of bacterial toxins, e.g. leucozidin, streptolysine. The strategies which the pathogenic bacteria employ in their efforts to occupy the host include adherence, penetration and multiplication, antiphagocytosis and serum resistance, the formation of siderophores, antiimmunity, and cell and tissue damage. An attempt will be made here to present an overview of this multifactorial event in which the host obviously plays an important role.
 ...
PMID:Relevance, pathogenicity and virulence of microorganisms in implant related infections. 903 48

We recovered an unusual bacterial strain from blood or sputum of three patients with septicemia, endocarditis, and/or respiratory failure. The three isolates were thin, curved, gram-negative, light brown, pigment-producing bacilli with variable catalase activity. They were asaccharolytic, oxidase-negative, nonmotile, and fastidious. Identification was not possible on the basis of these characteristics alone or in combination with cellular fatty acid profiles. Nucleic acid amplification and sequence analysis of the 16S rRNA gene revealed that all three isolates were identical and most closely related to the emerging pathogen Bordetella holmesii, diverging from the published sequence at three nucleotide positions (99.8% similarity). Isolation of a B. holmesii-like pathogen from sputum suggests that, in addition to producing septicemia, the organism may inhabit the respiratory tract like other Bordetella species.
 ...
PMID:Bordetella holmesii-like organisms associated with septicemia, endocarditis, and respiratory failure. 950 60

Sepsis is believed to increase the risk of bilirubin brain toxicity, but the mechanism is not known. Adult male Sprague-Dawley rats were injected intraperitoneally with either 20 mg/kg Escherichia coli lipopolysaccharide, approximately 5 x 10(9)/kg CFU Listeria monocytogenes or vehicle 48 h prior to sacrifice. Rats were killed with an intraperitoneal injection of pentobarbital. Mitochondrial membrane fractions were produced by homogenization of the brains and differential centrifugation in 0.32 M sucrose. The mitochondrial pellet was resuspended in distilled water and sonicated to rupture the mitochondria. The protein concentration of the suspension was standardized to 2.5 mg/ml. Bilirubin oxidation was assayed in a pH 8.2, 0.1 M barbital buffer containing 10 microM bilirubin, 5 mM EDTA, and 500 U/ml catalase. Optical density was measured at 440 nm before and after a 60-min incubation at 37.5 degrees C. There were no differences between the control, endotoxemic, and septic groups as far as the ability of brain mitochondrial membranes to oxidize bilirubin (bilirubin oxidation rate: 289 +/- 11 vs. 295 +/- 9 vs. 296 +/- 12 pmol/min/mg protein, mean +/- SD). We conclude that endotoxemia or sepsis do not change the ability of brain mitochondrial membranes to oxidize bilirubin. If sepsis truly increases the risk of bilirubin encephalopathy in neonatal jaundice, this is likely to involve other mechanisms.
 ...
PMID:Effects of endotoxemia and sepsis on bilirubin oxidation by rat brain mitochondrial membranes. 957 65

The purpose of this review-hypothesis is to discuss the literature which had proposed the concept that the mechanisms by which infectious and inflammatory processes induce cell and tissue injury, in vivo, might paradoxically involve a deleterious synergistic 'cross-talk', among microbial- and host-derived pro-inflammatory agonists. This argument is based on studies of the mechanisms of tissue damage caused by catalase-negative group A hemolytic streptococci and also on a large body of evidence describing synergistic interactions among a multiplicity of agonists leading to cell and tissue damage in inflammatory and infectious processes. A very rapid cell damage (necrosis), accompanied by the release of large amounts of arachidonic acid and metabolites, could be induced when subtoxic amounts of oxidants (superoxide, oxidants generated by xanthine-xanthine oxidase, HOCl, NO), synergized with subtoxic amounts of a large series of membrane-perforating agents (streptococcal and other bacterial-derived hemolysins, phospholipases A2 and C, lysophosphatides, cationic proteins, fatty acids, xenobiotics, the attack complex of complement and certain cytokines). Subtoxic amounts of proteinases (elastase, cathepsin G, plasmin, trypsin) very dramatically further enhanced cell damage induced by combinations between oxidants and the membrane perforators. Thus, irrespective of the source of agonists, whether derived from microorganisms or from the hosts, a triad comprised of an oxidant, a membrane perforator, and a proteinase constitutes a potent cytolytic cocktail the activity of which may be further enhanced by certain cytokines. The role played by non-biodegradable microbial cell wall components (lipopolysaccharide, lipoteichoic acid, peptidoglycan) released following polycation- and antibiotic-induced bacteriolysis in the activation of macrophages to release oxidants, cytolytic cytokines and NO is also discussed in relation to the pathophysiology of granulomatous inflammation and sepsis. The recent failures to prevent septic shock by the administration of only single antagonists is disconcerting. It suggests, however, that since tissue damage in post-infectious syndromes is caused by synergistic interactions among a multiplicity of agents, only cocktails of appropriate antagonists, if administered at the early phase of infection and to patients at high risk, might prevent the development of post-infectious syndromes.
 ...
PMID:Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae? 1049 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>